APPLICANT'S ABSTRACT: Recent studies document the negative impact of prenatal cocaine use on pregnancy outcome. While some data are available suggesting additional negative effects of prenatal cocaine use on the neuro development of the infant and child, few studies have explored the impact of cocaine exposure on other developing organ systems. In particular, no studies have been published investigating the immunopharmacologic effects of cocaine on the exposed fetus. Additionally, few data exist defining the metabolism of cocaine by the developing fetus and the potential effects of the parent compound or its metabolites on outcome. The principal investigator hypothesizes that the fetus and premature neonate lack the metabolic capacity to convert cocaine to benzoylecgonine (BZE), the major metabolic product of cocaine produced by adults. The principal investigator also hypothesizes that prenatal cocaine use inhibits the development of the fetal immune system, predisposing the neonate to the contraction of various disease states. The initial steps toward testing these hypotheses include the following specific aims: 1) Determine the types and quantities of metabolites detectable in a variety of biological specimens (cord blood, amniotic fluid, infant urine, infant meconium, umbilical cord tissue, maternal hair) using an immunoassay technique and high performance liquid chromatography with gas chromatography- mass spectrometry (HPLC-GC/MS). 2) Explore the immunopharmacologic impact of cocaine and metabolites on the fetal immune system. Eighty subjects will been erolled with 40 identified by history as cocaine users and 40 as non-cocaine users. Detailed drug histories will be obtained. All biological samples will be analyzed for cocaine and metabolites and comparisons made to each other and to maternal history. Cord blood and maternal blood will be analyzed for the immunopharmacologic effects of cocaine and metabolites on the newborn. The body of knowledge gained from this research should provide a better understanding of fetal cocaine metabolism which in turn should provide a focus for the development of suitable strategies for the identification of cocaine exposed babies. In addition, this study will provide data regarding the effect of prenatal cocaine use on the fetal immune system which will provide the preliminary data needed to pursue the long-term goal of determining the relationship between fetal cocaine exposure and immune suppression.